Although recommended for cardiovascular (CV) risk stratification in adults, the role of lipoprotein(a) [Lp(a)] in hypertension is not fully established. To evaluate Lp(a) levels in adult outpatients with essential arterial hypertension. A retrospective, observational study was conducted in outpatients of both sexes, aged ≥ 18 years, with treated or untreated essential hypertension, who were consecutively evaluated at the Hypertension Unit, Excellence Hypertension Center, Sant’Andrea Hospital, Rome, Italy. Participants underwent office and out-of-office blood pressure (BP) measurements, as well as assessment of hypertension-mediated organ damage (HMOD). BP measurements were performed, and hypertension phenotypes were classified according to 2023 European hypertension guidelines. Lp(a) levels were measured, and the study population was stratified according to a Lp(a) cut-off value of ≥50 mg/dl. Due to the non-uniform distribution, absolute Lp(a) values were logarithmically transformed. A total of 230 patients with available Lp(a) values were included (42.6

Previous experimental studies showed that dysfunctions of mitofusin 2 (Mfn2), a mitochondrial dynamin-related protein, are associated with the presence of left ventricular hypertrophy (LVH). We examined the association of MFN2/rs2336384 and MFN2/rs2236057 polymorphic variants with the presence of LVH in three-hundred-forty-five patients with essential hypertension. One-hundred-thirteen individuals (33%) presented LVH. Hypertensive patients carrying the GG genotype at the MFN2/rs2336384 had a significant increase of echocardiographically-assessed septal thickness, posterior wall thickness, relative wall thickness (RWT), LV mass/ body surface area (BSA) (p = 0.001), LV mass/height2, and left atrium volume index (LAVi) compared to subjects carrying either TT or TG genotypes. These results were confirmed after adjustment for age, gender, body mass index (BMI), office blood pressure (BP), antihypertensive treatment with a combination of two or more drugs and the number of BP-lowering agents. With regard to MNF2/rs2236057, hypertensive subjects carrying the mutant A allele had a significant increase of septal thickness, posterior wall thickness, RWT, LV mass/BSA, LV mass/height2 and LAVi compared to wild-type homozygotes (GG genotype) and heterozygotes (GA genotype). After adjustment for covariates, the results were still significant for septal thickness, posterior wall thickness, LV mass/BSA and LAVi. Multivariable logistic regression analysis demonstrated that the carrier status of both G allele at rs2336384 and A allele at rs2236057 was associated with an increased risk of LVH. Our results demonstrate a significant association of MFN2 variants with LVH in hypertensives and highlight the potential role of MFN2-dependent mitochondrial dysfunction on increased susceptibility to cardiac damage in human hypertension. Relationship between Mitofusin 2 polymorphisms and left ventricular hypertrophy. CI, confidence interval; LVH, left ventricular hypertrophy; MFN2, mitofusion 2; OR, odds ratio.

BACKGROUND:Quantitative flow ratio (QFR) is effective in predicting mortality in patients undergoing transcatheter aortic valve replacement (TAVR). How QFR reclassifies coronary artery disease (CAD) at vessel-level compared to angiography and how this influences the risk of death, remains undetermined. METHODS:We calculated QFR from consecutive 280 TAVR patients with bystander coronary stenoses. All lesions were managed conservatively. Angiographic CAD was defined by a diameter stenosis ≥ 50%, functional CAD by a QFR ≤ 0.80. The outcome was mortality at 3 years. RESULTS:Overall, 635 lesions were included. Angiographic CAD was evident in 165 (26.0%), functional CAD in 17 (11.2%) (reclassification: p < 0.001). Angiography/QFR mismatch occurred in 22.5%, mostly in large vessels and lesions located in the proximal left anterior descending (LAD). QFR ≤ 0.80 was an independent predictor of death (HR 2.91, 95% CI 1.94-4.36; p < 0.001). The risk was progressively increased for lower QFR values and positive QFR at LAD site (vs. QFR > 0.80 HR: 3.92, 95% CI 2.78-5.53; p < 0.001; vs. QFR ≤ 0.80 at non-LAD site: HR 2.65, 95% CI 1.07-6.59; p = 0.034). CONCLUSIONS:QFR leads to a significant reclassification of CAD rates at vessel-level and shows a significant prognostic value in patients undergoing TAVR.

Acute myocardial ischaemic syndromes frequently arise from rupture or erosion of non-flow-limiting vulnerable plaques. Despite major advances in lipid-lowering and anti-inflammatory therapies, a substantial residual cardiovascular risk persists under optimal medical therapy, driving interest in preventive percutaneous coronary intervention (PCI) to stabilize these high-risk lesions. Contemporary intracoronary imaging techniques, including intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy, can identify plaques at greatest risk of rupture, and preventive PCI, as demonstrated in the PREVENT trial, may reduce composite outcomes of cardiac death, myocardial infarction, revascularization, and unstable angina compared with medical therapy alone. Sealing such plaques may prevent future acute coronary events, particularly in high-risk patients with multivessel disease. However, these benefits were driven mainly by softer endpoints observed in an open-label design, and were not accompanied by significant reductions in mortality or hard outcomes. Concerns remain regarding the procedural risks and cost-effectiveness of preventive PCI, and the impact of novel and more intensive lipid-lowering therapies in this clinical setting has not been adequately explored. Although preventive PCI represents an intriguing paradigm shift that challenges physiology-guided treatment strategies, further studies are needed to confirm its safety, durability, and incremental value over contemporary medical therapy. This Great Debate examines whether preventive PCI should be considered the default management strategy for non-flow-limiting vulnerable plaques.

Patients with difficult to control hypertension (HTN) are often referred by general practitioners to specialized centers to estimate global cardiovascular (CV) risk profile, evaluate hypertension-mediated organ damage (HMOD), and optimize antihypertensive therapy. This referral provides a unique opportunity to analyse patients with high CV risk and HTN in a real-world setting, characterized by the rigorous adoption of uniform and state-of-the-art procedures by expert personnel. To examine (1) global CV risk profile, office and out-of-office blood pressure (BP) levels, and markers of HMOD in adult patients referred to a high-volume European Hypertension center; (2) to evaluate how these clinical parameters impact on the choice of different antihypertensive therapies. An observational, cross-sectional study was conducted in adult patients of both sexes, aged ≥ 18 years, with essential treated hypertension, who were consecutively evaluated at the Excellence Hypertension Center at Sant’Andrea Hospital in Rome, Italy. Office and out-of-office BP levels were measured, and different hypertension phenotypes were set according to European guidelines. CV risk profile was estimated according using SCORE2. Only patients with treated HTN were selected for the analysis and stratified according to antihypertensive therapies: (1) angiotensin receptor blockers (ARBs); (2) angiotensin converting enzyme (ACE) inhibitors; (3) other drugs (including diuretics, beta-blockers, calcium channel blockers, alpha-blockers, mineralocorticoid receptor antagonists). From an overall database of 11,168 outpatients, a total of 5,677 patients with treated HTN were analysed (46.3

BACKGROUND:Tricuspid regurgitation (TR) is a progressive and underdiagnosed condition associated with poor prognosis. Although the TRI-SCORE is a validated risk model for patients undergoing tricuspid valve surgery, it does not incorporate echocardiographic measures of right ventricular (RV) function or RV-pulmonary artery coupling, which are increasingly recognised as major prognostic determinants. OBJECTIVES:To evaluate whether integration of simple, widely available echocardiographic indices-tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP), TAPSE/RV end-diastolic area (RVAD) and TAPSE/RV end-systolic area (RVAS)-improves the prognostic performance of the TRI-SCORE in patients with moderate-to-severe TR. METHODS:We retrospectively included 93 patients with severe TR, including functional, mixed and primary/Cardiac Implantable Electronic Device (CIED)-related aetiologies treated with medical therapy, surgery or transcatheter edge-to-edge repair. The primary endpoint was all-cause mortality; the secondary endpoint was a composite of mortality or heart failure hospitalisation. Multivariable Cox regression models were used to assess the incremental predictive value of each TAPSE-derived ratio beyond the TRI-SCORE. Optimal thresholds were derived using spline regression and maximally selected rank statistics. RESULTS:Lower TAPSE/PASP, TAPSE/RVAD and TAPSE/RVAS values were independently associated with worse outcomes. Each parameter significantly enhanced risk discrimination when added to the TRI-SCORE (C-index improved from 0.614 to 0.710 for TAPSE/PASP, 0.685 for TAPSE/RVAD and 0.696 for TAPSE/RVAS; all p<0.001). Prognostically relevant cut-offs were identified at 0.44, 0.80 and 1.3, respectively. CONCLUSIONS:Simple echocardiographic indices of RV function provide substantial incremental prognostic value when combined with the TRI-SCORE and may improve risk stratification and timing of intervention in isolated TR.

BACKGROUND:In the assessment of coronary physiology, non-hyperemic pressure ratios (NHPRs) provide an alternative to fractional flow reserve (FFR) without the need for hyperemic agents, reducing procedural time, side effects, and costs. However, it remains unclear whether NHPRs have similar diagnostic performance in the different coronary arteries. This study evaluates the diagnostic performance of NHPRs compared with FFR, stratified by coronary artery, in stable patients with coronary artery disease. METHODS:We conducted a systematic review and individual patient-level data meta-analysis from prospective studies involving patients with intermediate to severe coronary stenosis who underwent physiological assessment with NHPRs and FFR. NHPRs included resting full-cycle ratio or instantaneous wave-free ratio (iFR). The diagnostic performance of NHPRs was calculated using a threshold of ≤0.89 for NHPRs with FFR ≤0.80 as the reference and by stratifying between the left anterior descending artery (LAD) and non-LAD vessels. RESULTS:A total of 2120 paired FFR and NHPRs (1257 resting full-cycle ratio, 863 iFR) measurements were analyzed. The LAD artery was the interrogated vessel in 67% of cases, the left circumflex artery in 15%, and the right coronary artery in 17%. The mean NHPR and FFR values were 0.80±0.17 and 0.71±0.14, respectively. The overall sensitivity, specificity, and accuracy of NHPRs were 82%, 86%, and 83%. In non-LAD vessels, NHPRs had significantly lower sensitivity and accuracy, but higher specificity compared with LAD (69% versus 87%, 76% versus 86%, and 91% versus 81%, respectively, P<0.001 for all). The optimal NHPRs cutoff for detecting significant lesions differed between LAD (≤0.88) and non-LAD (≤0.92). CONCLUSIONS:NHPRs demonstrated lower diagnostic performance in non-LAD vessels compared with the LAD. These results underscore the need for vessel-specific interpretation of NHPR measurements.

BACKGROUND AND AIMS:Micro- and nanoplastics (MNPs) are emerging risk factors for cardiovascular diseases. The present study aimed to evaluate the burden of MNPs in coronary blood across the spectrum of coronary artery disease (CAD), and their association with air pollution exposure and inflammation. METHODS:Cross-sectional study, including 61 consecutive patients undergoing coronary angiography for suspected CAD, stratified into: ST-segment elevation myocardial infarction (STEMI, n = 19), chronic coronary syndromes (CCS, n = 20), and controls with normal coronary arteries (n = 22). MNPs were quantified in coronary and peripheral blood using pyrolysis-gas chromatography-mass spectrometry and laser direct infrared spectroscopy. Air pollution exposure data were collected on the day of the invasive procedure (acute exposure) and over the preceding 2 years (chronic exposure). RESULTS:MNPs were detected significantly more frequently in STEMI patients (84.2%) than in CCS (40%) and controls (31.8%) (P = .002), with higher concentration and greater polymer diversity [median of 3 polymers (interquartile range: 2-4), P < .001]. Polyethylene was the predominant polymer (97%). The same polymers were consistently identified in peripheral and coronary blood samples from individual patients, with the highest concentrations in coronary blood (P < .001). STEMI patients showed higher levels of interleukin-6 and tumour necrosis factor-α (P≤.006) and were exposed to higher levels of PM2.5 (P≤.012). MNP detection was more frequent among smokers and patients exposed to PM2.5 > 15 µg/m3 (P = .006), with all patients presenting both factors showing detectable MNPs (P < .001). In multivariable analysis, smoking history emerged as the only independent predictor of MNP presence (odds ratio 5.69, 95% confidence interval 1.33-26.63, P = .023). CONCLUSIONS:STEMI patients exhibited a greater burden of MNPs in coronary blood than CCS and controls. MNP detection frequently co-occurred with elevated inflammatory biomarkers, greater PM2.5 exposure, and smoking, suggesting a potential association between environmental exposure and CAD.

BACKGROUND:Contemporary self-expanding transcatheter heart valves (THVs) differ in leaflet position and frame architecture. Comparative data between new-generation intra-annular (IA) and supra-annular (SA) platforms remain limited. AIMS:We sought to compare 30-day and 1-year clinical and haemodynamic outcomes between contemporary intra-annular and supra-annular self-expanding THVs in a large multicentre real-world cohort. METHODS:Consecutive patients undergoing transfemoral transcatheter aortic valve implantation with a Navitor/Navitor Vision (IA self-expanding valve [SEV]) or Evolut FX/FX+ (SA-SEV) between June 2021 and April 2025 were included. The primary endpoint was the composite of all-cause death, disabling stroke, or heart failure hospitalisation at 1 year. Propensity score matching (PSM) was performed to adjust for baseline differences. RESULTS:Among 2,607 patients (IA-SEV: 1,604; SA-SEV: 1,003), PSM yielded 892 well-balanced pairs. Valve Academic Research Consortium 3 device success was achieved in 91.1% of IA-SEV patients and 90.9% of SA-SEV patients (p=0.868). Permanent pacemaker implantation was more frequent with IA-SEVs (22.1% vs 16.3%; p=0.007), whereas major or life-threatening bleeding was more common with SA-SEVs (4.2% vs 2.6%; p<0.001). At 1 year, the primary endpoint occurred in 12.6% of IA-SEV patients and 11.3% of SA-SEV patients (p=0.422) with no difference between groups in the time-to-event analysis (hazard ratio [HR] 1.01, 95% confidence interval [CI]: 0.77-1.33; p=0.916). The mean transvalvular gradients and rates of moderate or severe paravalvular leak remained low and similar between the two groups at 1 year. Findings were consistent in the unmatched cohort (HR 1.02, 95% CI: 0.81-1.31; p=0.835). CONCLUSIONS:In this large real-world registry, contemporary IA-SEVs and SA-SEVs demonstrated overall similar clinical outcomes and sustained haemodynamic performance at 1-year follow-up, despite differences in procedure-related endpoints between the groups.

BACKGROUND:The tenet of cardiac amyloidosis (CA) as a paradigm of heart failure with restrictive ventricular physiology and preserved systolic function has come under scrutiny. We aimed to evaluate the prevalence and clinical significance of left ventricular (LV) systolic dysfunction versus restriction in a large real-world cohort with CA, assessed at the time of diagnosis. METHODS:We retrospectively analyzed 540 TTR (transthyretin)-CA and 280 AL (light chain)-CA. Patients were divided into 3 LV phenotypes: (1) preserved LV function: LV ejection fraction >40% associated with grade I diastolic dysfunction; (2) restriction: LV ejection fraction >40% associated with grade II/III diastolic dysfunction; (3) systolic dysfunction: LV ejection fraction ≤40% irrespective of diastolic function. We analyzed the progression from preserved LV function towards the other 2 LV phenotypes and survival free from the composite end point of all-cause mortality and heart transplantation. RESULTS:In TTR-CA, the prevalence of preserved LV function was 32.0%, restriction was 56.1%, and systolic dysfunction was 11.9%. Among patients with preserved LV function, at the last evaluation, the conversion rate to restriction was 16.3% and to systolic dysfunction was 1.8%. The 3-year freedom from the composite end point was 75%, 61%, and 44%, respectively. In AL-CA, the prevalence of preserved LV function was 32.9%, restriction was 58.6%, and systolic dysfunction was 8.5%. Among patients with preserved LV function, at the last evaluation, the conversion rate to restriction was 12.9%, and to systolic dysfunction was none. The 3-year freedom from the composite end point was 46%, 32%, and 21%, respectively. CONCLUSIONS:Restriction was the most common presenting phenotype, while preserved LV function represented approximately one-third. The rate of progression from preserved LV function towards restriction was high, whereas it was limited towards systolic dysfunction. Although patients with preserved LV function presented the best event-free survival, considering all-cause mortality and heart transplantation, compared with restriction or systolic dysfunction, these phenotypes are not independent predictors of this composite end point.

Microplastics are emerging as mediators in the interaction between environmental pollutants and cardiovascular health. Micro- and nanoplastics (MNPs) can enter the human body through ingestion, inhalation, or skin exposure, disrupting biological processes such as autophagy, inflammation, oxidative stress, immune activation, and vascular dysfunction. Therefore, MNPs might promote the development of cardiovascular diseases. The link between MNPs and cardiovascular diseases remains unclear, with no consistent data confirming a correlation between their concentration in tissues and disease onset. Continuously evolving analytical techniques to detect MNPs within human organs and tissues will help the design of prospective studies detailing the possible harm provided by different microplastics as well as their effects according to their physical properties and associated chemicals. In this review, we provide an update on the existing techniques for MNP detection and characterization to summarize the mechanisms linking these pollutants to human health, focusing on their effects on the cardiovascular system.

Aims Cardiopulmonary exercise testing (CPET) parameters are used for heart failure (HF) prognostication. While the ventilation to carbon dioxide production (VE/VCO2) slope ≥34 identifies high risk, patients with intermediate values remain heterogeneous. The VE/VCO2 Y-intercept, reflecting dead space ventilation at rest and its changes during effort, may refine prognostication.Methods We retrospectively analysed 2642 HF. Follow-up was 26 (9–63) months. The study endpoint was the composite of all-cause death, urgent transplant or left ventricular assist device implantation.Results Median age was 62 (53–70) years and left ventricular ejection fraction (LVEF) 33% (27%–39%). 27% of patients were New York Heart Association class III–IV. During follow-up, 534 events occurred. Both VE/VCO₂ slope and peakVO₂ were associated with outcome in univariable and multivariable models (HR 1.04, 95% CI 1.03 to 1.06; HR 0.90, 95% CI 0.88 to 0.93, p<0.001, respectively). Y-intercept was not prognostic univariately but added independent value in multivariable models (HR 1.08, 95% CI 1.04 to 1.13, p<0.001). Prognosis and clinical profiles improved from group A (VE/VCO2 slope ≥34, n=858) to B (28–34, n=943) to C (<28, n=841). Group A versus C patients had lower LVEF (30% (25%–36%) vs 35% (30%–40%), ptrend<0.001), peakVO₂ (12.7 (10.06–15.3) vs 17.7 (14.6–21.6) mL/kg/min, ptrend<0.001) and higher N-terminal pro-B-type natriuretic peptide (1400 (572–3122) vs 454 (174–1081) pg/mL, ptrend<0.001). Only within group B, a high median Y-intercept (B1≥3.9 L/m) clearly identified patients with higher HF severity and worse survival than B2 (<3.9 L/m, log-rank p<0.001).Conclusion An increase in the VE/VCO2 slope is associated with a progressive lower survival. Y-intercept enhances risk assessment in HF with intermediate VE/VCO₂ slope values.

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) exerts pleiotropic metabolic and anti-inflammatory effects, but its role in calcific aortic valve stenosis (CAVS) is unclear. In this multicenter prospective study, 83 patients with severe CAVS undergoing surgical aortic valve replacement were stratified by SGLT2i use. Explanted valve tissue and plasma were analyzed using transcriptomics, circulating biomarkers, and metabolomics, including MALDI-MSI. SGLT2i therapy was associated with reduced valvular expression of SGLT1/2, GLUT4, and NHE, increased PPARα, decreased PPARγ, attenuation of inflammatory signaling (lower NF-κB and IL-6), and oxidative stress response (higher SOD2). Extracellular matrix turnover and fibrocalcific remodeling enzymes (MMP-9 and MMP-12) were also reduced. Metabolomic profiling demonstrated distinct clustering, with enrichment of amino acid and redox pathways in SGLT2i users. These findings suggest that SGLT2i therapy is associated with coordinated molecular and metabolic reprogramming of the valvular microenvironment, supporting a potential disease-modifying role in CAVS.

Percutaneous coronary procedures performed in a day-case setting are intended to facilitate an optimised resource allocation and increase patient satisfaction without compromising procedural and long-term safety or efficacy. While an increasing number of centres have implemented a day-case approach, patient pathways and procedural aspects still lack standardisation, potentially leading to a large heterogeneity in practices. However, several centres and healthcare systems are still reluctant to adopt day-case diagnostic or therapeutic coronary procedures because of safety concerns, penalising reimbursement policies, or simple inertia. This clinical consensus statement summarises experience-based know-how and research-derived data on day-case coronary procedures with the objective of providing standardised practical guidance on patient selection, procedural considerations, and postprocedural management to facilitate wide-scale adoption of a day-case coronary programme. The document also provides clear advice on when such procedures must be converted into regular admissions to maximise patient safety.